TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer.
TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer.
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TROP2 作为患者定制的乳腺癌生物标志物，但不是预后生物标志物
DOI：
10.2147/ott.s354048
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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滋养层细胞表面抗原2（TROP 2）已经成为用于三阴性乳腺癌（TNBC）以及其他乳腺癌（BC）的抗体-药物缀合物（ADC）的有希望的靶标。本研究旨在研究TROP 2的生物标志物价值，用于BC患者（包括TNBC）的患者定制和预后。采用免疫组织化学方法检测404例中国人乳腺癌组织中TROP 2的表达水平，并分析其与临床病理因素和总生存率的关系。此外，使用具有不同TR 0 P2表达水平的BC细胞系和患者来源的类器官（PDO）来研究TR 0 P2表达水平与对DS 001（具有稳定接头和有效有效负载的TR 0 P2导向的ADC分子）的治疗应答之间的相关性。TROP 2过表达在显著多于（P = 0.046），TNBC组（59.38%，19/32）显著高于其他类型（38.28%，80/209）。具有最低TROP 2表达水平的BC细胞系对DS 001处理没有应答。TR 0 P2的表达水平被确定为与DS 001治疗的效力显著相关，但与患者的总体存活率无关。我们的结果表明，TR 0 P2可以作为ADC治疗的患者定制和预测生物标志物，但不能作为预测患者生存的一般预后生物标志物。
Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic for BC patients, including TNBC. The levels of TROP2 expression in 404 Chinese BC tissues on tissue microarrays (TMAs) were quantified by immunohistochemistry and their correlations to the clinicopathological factors and the overall survival rate were analyzed. Also, BC cell lines and patient-derived organoids (PDOs) with different TROP2 expression levels were employed to investigate the correlation between TROP2 expression levels and the therapeutic responses to DS001, a TROP2-directed ADC molecule with stable linker and potent payload. TROP2 overexpression was identified in significantly more (P = 0.046) tumor tissues (41.08%, 99/241) than normal adjacent tissues (31.29%, 51/163) from Chinese BC patients, and in significantly more (P = 0.024) TNBC patients (59.38%, 19/32) than in other BC types (38.28%, 80/209). BC cell line with the lowest TROP2 expression level failed to respond to DS001 treatment. The levels of TROP2 expression were determined to be significantly correlated with the potencies of DS001 treatment, but not with the overall survival rates of the patients. Our results demonstrated that TROP2 could serve as a patient-tailoring and predictive biomarker for ADC therapeutics but not as a general prognostic biomarker to predicate patient survival.